This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV-1 infection emerged in Central Africa 50/60 years ago from a simian source (SIVcpz from chimpanzees). At least 3 cross-species transmission events have occurred, generating groups M, N and O. All three HIV-1 groups co-circulate in Cameroon. The mechanism of HIV emergence is unknown. In this regard, we have investigated the evidence of SIV infections in samples collected from humans in rural Cameroon. Methods. Plasma, cells, and matched syringe washes were collected from 1536 individuals and tested by Determine (Abbott,) rapid test and Inno-Lia Immunoblot (Innogenetics) as screening tests. All the samples showing reactivities in InnoLia were retested in an SIV specific peptide assay which contains both gp41 and V3 peptides. Our results confirmed that HIV-1 group M is the main viral form in Cameroon. We have identified HIV-1 group O in less than 5% of samples. Interestingly 7% of the tested samples, while negative by determine and indeterminate by InnoLia showed anti-SIV reactivities. These samples reacted with SIVcpz, SIVrcm and SIVmnd-2 peptides. None of these samples were positive by PCR suggesting the clearance of SIV infection after cross-species transmission. In conclusion, we have demonstrated that cross-species transmission of SIV to humans may occur in the epicenters of HIV pandemic. However, as suggested by our results, direct cross-species transmitted viruses appear to be cleared by the human host.